Sitagliptin prevents the development of metabolic and hormonal disturbances, increased B-cell apoptosis and liver steatosis induced by a fructose-rich diet in normal rats.

MAIZTEGUI B; BORELLI MI; MADRID V; DEL ZOTTO H; RASCHIA MA; FRANCINI F; MASSA ML; FLORES LE; REBOLLEDO O; GAGLIARDINO JJ

CLINICAL SCIENCE (LONDON, ENGLAND : 1979)

PORTLAND PRESS LTD

Lugar: Londres; Año: 2011 vol. 120 p. 73 - 80

0143-5221

The aim of this study was to test the effect of sitagliptin and exendin-4 upon metabolic alterations, β-cell mass decrease and hepatic steatosis induced by F (fructose) in rats. Normal adult male Wistar rats received a standard commercial diet without (C) or with 10% F in the drinking water (F) for 3 weeks; animals from each group were randomly divided into three subgroups: untreated (C and F) and simultaneously receiving either sitagliptin (CS and FS; 115.2 mg/day/rat) or exendin-4 (CE and FE; 0.35 nmol/kg body wt, ip). Water and food intake, oral glucose tolerance, plasma glucose, triglyceride, insulin and fructosamine concentration, HOMA-IR, HOMA-β and liver triglyceride content were measured. Pancreas immunomorphometric analyses were also performed. IGT (impaired glucose tolerance), plasma triglyceride, fructosamine and insulin levels, HOMA-IR and HOMA-β indexes, and liver triglyceride content were significantly higher in F rats. Islet β-cell mass was significantly lower in these rats, due to an increase in the percentage of apoptosis. The administration of exendin-4 and sitagliptin to F animals prevented the development of all the metabolic disturbances and the changes in β-cell mass and fatty liver. Thus, these compounds – useful to treat type 2 diabetes – would also prevent/delay the progression of early metabolic and tissue markers of this disease.